Our investigations with the epigenetic drug, zebularine, an inhibitor of DNA methylation continue. The article published last year (Cancer Prevention Res. 2008, 1, 233-240) provided strong data in support of epigenetic therapy in cancer prevention. Therefore, in order to explore the effects of zebularine following chronic administration, funds for a new in vivo study in mice using two human xenografts: NSCLC and Bladder carcinoma have been approved. This will be done using oral zebularine and a parallel pharmacokinetic (PK) study. Because the metabolism of zebularine by aldehyde oxidase (AO) is minimal in female mice, this study will use only female mice. Combined used of an AO inhibitor (Raloxifene) with zebularine is also contemplated. A new study that sheds light on the mechanism of zebularine has been published (Biochemical Pharmacology 2009, 78, 633641). the methylation inhibitor.